Source:http://linkedlifedata.com/resource/pubmed/id/20008139
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2009-12-30
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| pubmed:abstractText |
Transforming growth factor-beta cooperates with oncogenic Ras to activate nuclear beta-catenin during the epithelial to mesenchymal transition of hepatocytes, a process relevant in the progression of hepatocellular carcinoma (HCC). In this study we investigated the role of beta-catenin in the differentiation of murine, oncogene-targeted hepatocytes and in 133 human HCC patients scheduled for orthotopic liver transplantation. Transforming growth factor-beta caused dissociation of plasma membrane E-cadherin/beta-catenin complexes and accumulation of nuclear beta-catenin in Ras-transformed, but otherwise normal hepatocytes in p19(ARF)-/- mice. Both processes were inhibited by Smad7-mediated disruption of transforming growth factor-beta signaling. Overexpression of constitutively active beta-catenin resulted in high levels of CK19 and M2-PK, whereas ablation of beta-catenin by axin overexpression caused strong expression of CK8 and CK18. Therefore, nuclear beta-catenin resulted in dedifferentiation of neoplastic hepatocytes to immature progenitor cells, whereas loss of nuclear beta-catenin led to a differentiated HCC phenotype. Poorly differentiated human HCC showed cytoplasmic redistribution or even loss of E-cadherin, suggesting epithelial to mesenchymal transition. Analysis of 133 HCC patient samples revealed that 58.6% of human HCC exhibited strong nuclear beta-catenin accumulation, which correlated with clinical features such as vascular invasion and recurrence of disease after orthotopic liver transplantation. These data suggest that activation of beta-catenin signaling causes dedifferentiation to malignant, immature hepatocyte progenitors and facilitates recurrence of human HCC after orthotopic liver transplantation.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
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| pubmed:issn |
1525-2191
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| pubmed:author |
pubmed-author:BeugHartmutH,
pubmed-author:Grasl-KrauppBettinaB,
pubmed-author:HuberHeidemarieH,
pubmed-author:MikulaMarioM,
pubmed-author:MikulitsWolfgangW,
pubmed-author:Peck-RadosavljevicMarkusM,
pubmed-author:SchnellerDorisD,
pubmed-author:SieghartWolfgangW,
pubmed-author:WaldhörThomasT,
pubmed-author:ZulehnerGudrunG,
pubmed-author:van ZijlFranziskaF
|
| pubmed:issnType |
Electronic
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| pubmed:volume |
176
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
472-81
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| pubmed:dateRevised |
2011-4-6
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| pubmed:meshHeading |
pubmed-meshheading:20008139-Animals,
pubmed-meshheading:20008139-Cadherins,
pubmed-meshheading:20008139-Carcinoma, Hepatocellular,
pubmed-meshheading:20008139-Cell Differentiation,
pubmed-meshheading:20008139-Cell Membrane,
pubmed-meshheading:20008139-Cell Nucleus,
pubmed-meshheading:20008139-Epithelium,
pubmed-meshheading:20008139-Female,
pubmed-meshheading:20008139-Hepatocytes,
pubmed-meshheading:20008139-Humans,
pubmed-meshheading:20008139-Liver,
pubmed-meshheading:20008139-Liver Neoplasms,
pubmed-meshheading:20008139-Liver Transplantation,
pubmed-meshheading:20008139-Male,
pubmed-meshheading:20008139-Mesoderm,
pubmed-meshheading:20008139-Mice,
pubmed-meshheading:20008139-Neoplasm Recurrence, Local,
pubmed-meshheading:20008139-Neovascularization, Pathologic,
pubmed-meshheading:20008139-Phenotype,
pubmed-meshheading:20008139-Protein Transport,
pubmed-meshheading:20008139-Signal Transduction,
pubmed-meshheading:20008139-Smad7 Protein,
pubmed-meshheading:20008139-Stem Cells,
pubmed-meshheading:20008139-Transforming Growth Factor beta,
pubmed-meshheading:20008139-beta Catenin
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| pubmed:year |
2010
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| pubmed:articleTitle |
Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence.
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| pubmed:affiliation |
Department of Internal Medicine I, Centre of Public Health, Medical University of Vienna, Vienna, Austria.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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